Insulin-like growth factor binding protein 4 loaded electrospun membrane ameliorating tendon injury by promoting retention of IGF-1

Tendon injury is one of the most common musculoskeletal disorders that impair joint mobility and lower quality of life. The limited regenerative capacity of tendon remains a clinical challenge. Local delivery of bioactive protein is a viable therapeutic approach for tendon healing. Insulin-like growth factor binding protein 4 (IGFBP-4) is a secreted protein capable of binding and stabilizing insulin-like growth factor 1 (IGF-1). Here, we applied an aqueous-aqueous freezing-induced phase separation technology to obtain the IGFBP4-encapsulated dextran particles. Then, we added the particles into poly (L-lactic acid) (PLLA) solution to fabricate IGFBP4-PLLA electrospun membrane for efficient IGFBP-4 delivery. The scaffold showed excellent cytocompatibility and a sustained release of IGFBP-4 for nearly 30 days. In cellular experiments, IGFBP-4 promoted tendon-related and proliferative markers expression. In a rat Achilles tendon injury model, immunohistochemistry and quantitative real-time polymerase chain reaction confirmed better outcomes by using the IGFBP4-PLLA electrospun mem-brane at the molecular level. Furthermore, the scaffold effectively promoted tendon healing in functional per-formance, ultrastructure and biomechanical properties. We found addition of IGFBP-4 promoted IGF-1 retention in tendon postoperatively and then facilitated protein synthesis via IGF-1/AKT signaling pathway. Overall, our IGFBP4-PLLA electrospun membrane provides a promising therapeutic strategy for tendon injury.

Automated summary

Tendon injury is a common musculoskeletal disorder that limits joint mobility and reduces quality of life. Insulin-like growth factor binding protein 4 (IGFBP-4) has been identified as a potential therapeutic protein for tendon healing. In this study, an electrospun membrane was fabricated using IGFBP4-encapsulated dextran particles and poly (L-lactic acid) (PLLA) solution, which showed excellent cytocompatibility and sustained release of IGFBP-4. In rat Achilles tendon injury model, this scaffold promoted tendon healing at molecular, functional, ultrastructural, and biomechanical levels, potentially through IGF-1/AKT signaling pathway. This study suggests that the IGFBP4-PLLA electrospun membrane holds promise as a therapeutic strategy for tendon injury.